I am a psychiatrist serving as director of the Massachusetts General Hospital (MGH) Center for Addiction Medicine (CAM) and Associate Professor of Psychiatry at Harvard Medical School (HMS). I have conducted NIDA sponsored patient oriented addiction research (POAR) since 1999. From 2001-2006, I was supported by a NIDA K23 award that enabled me to earn a masters degree in public health and to conduct mentored clinical research in nicotine dependence treatment. In 2005, I was asked to direct the MGH CAM and began to build a thriving clinical research program and to spend significant time mentoring junior investigators. My research has focused on discovery of novel pharmacologic and behavioral treatments for nicotine dependence in those with and without major psychiatric illnesses. I currently serve as principal investigator (PI) for two NIDA R01 and one NIDA R21 grant awards and am Co-PI and Project PI for the NIDA U01 Cooperative Drug Discovery for the Treatment of Nicotine Addiction (CDDG-ND). I have established a group of fifteen junior investigators working collaboratively in the context of my funded research to translate recent advances in neuroscience to the study and treatment of addictions. I work in a rich environment for clinical research. I receive no institutional support for mentoring and will be required curtail my mentoring effort in order to assume significant clinical responsibilities beginning in 2011. The K24 award will protect time that would otherwise be diverted to clinical responsibilities to allow me to continue to provide intensive ongoing mentorship to junior investigators in POAR and to spend more effort attracting excellent junior researchers to POAR, while devoting 45% effort to conducting independent, peer-reviewed POAR to discover novel treatments for nicotine dependence. My long term career objectives are: 1) To improve outcomes for adults with nicotine dependence by developing and testing novel pharmacologic and behavioral interventions and developing algorithms to tailor these interventions to increase cessation rates and reduce relapse in individuals;2) To improve our knowledge base of how to effectively treat nicotine dependence in smokers with co-morbid mental illness;3) To develop therapies for nicotine dependence that act upon basic mechanisms such that they are effective for other addictive disorders;and 4) To contribute to the development of early career investigators in clinical addiction research by providing mentored research opportunities. The specific aims to be accomplished during the period of the award are to 1) Develop specific expertise in clinical research applications of neuroimaging and genetics in order to enhance ongoing and future research in development and testing of novel treatments for prevention of relapse to smoking and development of a knowledge base to guide patient-centered nicotine dependence treatment. 2) Protect time for substantive mentoring of junior investigators. 3) Continue and extend involvement in POAR. To accomplish these goals, I will devote 20% effort to new training, 30% effort to substantive mentoring of junior investigators, and 45% effort to funded POAR. PUBLIC HEALTH RELEVANCE: Each year over 430,000 people in the US die from smoking-related illness;the annual global mortality toll is over 5 million, and 500 million existing cigarette smokers will die of causes that could be prevented by treatment of their addiction to tobacco-delivered nicotine. This K24 award will support mentoring and training of talented clinical scientists to discover novel treatments for smoking cessation and prevention of relapse to smoking that would not otherwise be supported.